The overall goal of this project is to understand the role of genetics in the etiology and prevention of upper gastrointestinal cancers (esophagus, gastric cardia, gastric body). The objective of current studies is to identify susceptibility genes for these cancers, beginning with cancer of the esophagus. Esophageal cancer is the 7th most common cause of cancer death worldwide. Several lines of evidence (family history, familial aggregation, segregation, cytogenetics) suggest that genetic factors may play an important role in the etiology of this malignancy. Identification of susceptibility genes may allow screening of populations to identify persons at particularly high risk who could then be targeted for prevention strategies (e.g., chemoprevention or early detection). Several studies are in progress or planning to study these cancers in persons from Shanxi Province, China, where rates are among the highest in the world, including collection of DNA for 1) a tumor/nontumor study of 450 cases, 2) a high-risk/low-risk population study of 200 subjects, 3) a case-control study of 1,400 cases and 1,400 controls, and 4) a linkage study in 150 families with multiple cases. DNA from over 200 tumor/nontumor cases have been collected, and candidate molecular analyses are in progress in a limited number of esophageal cancers; comparative genomic hybridization and microsatellite marker genomic scans will follow. The case-control and linkage studies were initiated in late 1996.